This multidisciplinary program project will explore the biology of the lymphocyte on a broad front. We will focus primarily on four areas. (1) Genetic control of lymphocyte surface antigens and immune responsiveness; mechanisms of antigen recognition and cellular differentiation leading to immunity or tolerance; cellular interactions involved in cell-mediated immunity -- all of which will use in vitro cell culture techniques, e.g., mixed leukocyte cultures, cell-mediated lympholysis, graft-versus-host reactions and others. (2) Lymphocyte susceptibility to murine leukemia virus both with respect to genetic factors controlling susceptibility and the phenotypic expression resulting from virus-cell interaction. (3) Lymphoid cell differentiation in the ontogeny of immunity. (4) Ultrastructure of various lymphocyte populations, especially using the one million volt electron microscope. The overriding purpose of this program is to integrate these various approaches and relate them to clinical immunobiological problems.